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US 11,453,676 B2Granted
Inhibitors of protein arginine deiminases
AssigneeForward Therapeutics, Inc.
InventorToufike Kanouni
Life of this patent
Estimating the term…
Abstract
Provided herein are inhibitors of protein arginine deiminases (PADs), pharmaceutical compositions comprising said the compounds, and methods for using the compounds for the treatment of diseases.
Claims17
A compound, or pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (I):
- wherein,
- R5 is selected from halogen;
- R6 is selected from fluoro;
- R7 is selected from fluoro;
- X is selected from:
- wherein n is 2, 3, or 4;
- each R1 is independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted cycloalkylalkyl;
- and each R2 is independently hydrogen or optionally substituted alkyl;
- wherein p is 1, 2, 3, or 4;
- q is 1, 2, 3, or 4;
- each R1 is independently selected from hydrogen, halogen, —OH, —NH2, optionally substituted alkyl, or optionally substituted alkoxy;
- each R2 is hydrogen or optionally substituted alkyl;
- and R3 is hydrogen or optionally substituted alkyl;
- wherein p is 1, 2, 3, or 4;
- q is 1, 2, 3, or 4;
- each R1 is independently selected from hydrogen, halogen, —OH, —NH2, optionally substituted alkyl, or optionally substituted alkoxy;
- each R2 is hydrogen or optionally substituted alkyl;
- and R3 is hydrogen or optionally substituted alkyl.
15 more elements
A compound, or pharmaceutically acceptable salt or solvate thereof, selected from:
- (R)-(3-Aminopyrrolidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone,
- (R)-(3-Aminopyrrolidin-1-yl)(5,6,7-trifluoro-1H-indol-2-yl)methanone,
- (R)-(3-Aminopyrrolidin-1-yl)(5-bromo-6,7-difluoro-1H-indol-2-yl)methanone,
- ((3 S,4R)-3-Amino-4-fluoro-pyrrolidin-1-yl)-(5-chloro-6,7-difluoro-1H-indol-2-yl)-methanone,
- (S)-N-(1-Aminopropan-2-yl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide,
- (S)-N-(1-Aminobutan-2-yl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide,
- N-(2-Amino-1-cyclopropylethyl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide,
- N-(3-(Aminomethyl)oxetan-3-yl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide,
- 5-Chloro-6,7-difluoro-N-((3 S,4R)-4-methylpyrrolidin-3-yl)-1H-indole-2-carboxamide,
- 5-Chloro-6,7-difluoro-N-((3 S,4S)-4-methylpyrrolidin-3-yl)-1H-indole-2-carboxamide,
- 5-Chloro-6,7-difluoro-N-((3R,4R)-4-hydroxypyrrolidin-3-yl)-1H-indole-2-carboxamide,
- 5-Chloro-6,7-difluoro-N-((3R,4S)-4-hydroxypyrrolidin-3-yl)-1H-indole-2-carboxamide,
- 5-Chloro-6,7-difluoro-N-((3 S,4R)-4-hydroxypyrrolidin-3-yl)-1H-indole-2-carboxamide,
- 5-Chloro-6,7-difluoro-N-((3 S,4S)-4-hydroxypyrrolidin-3-yl)-1H-indole-2-carboxamide,
- (S)-N-(1-Amino-4-methylpentan-2-yl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide,
- 5-Chloro-6,7-difluoro-N-((3R,4R)-4-methylpyrrolidin-3-yl)-1H-indole-2-carboxamide,
- (R)-N-(1-Aminopropan-2-yl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide, ((3 S,4S)-3-Amino-4-hydroxypyrrolidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone,
- N-(Azetidin-3-yl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide,
- (3-Aminoazetidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone,
- (R)-5-Chloro-6,7-difluoro-N-(pyrrolidin-3-yl)-1H-indole-2-carboxamide,
- (S)-5-Chloro-6,7-difluoro-N-(pyrrolidin-3-yl)-1H-indole-2-carboxamide,
- (S)-(3-Aminopyrrolidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone,
- (S)-N-(1-Amino-3,3-dimethylbutan-2-yl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide,
- (5-Chloro-6,7-difluoro-1H-indol-2-yl)((3 S,4S)-3,4-diaminopyrrolidin-1-yl)methanone,
- N-((3 S,4S)-4-Aminopyrrolidin-3-yl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide,
- N-((3R,4S)-4-Aminopyrrolidin-3-yl)-5-chloro-6,7-difluoro-1H-indole-2-carboxamide,
- ((3 S,4R)-3-Amino-4-hydroxypyrrolidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone,
- 5-Chloro-6,7-difluoro-N-((3 S,4S)-4-methoxypyrrolidin-3-yl)-1H-indole-2-carboxamide,
- 5-Chloro-6,7-difluoro-N-((3R,4R)-4-methoxypyrrolidin-3-yl)-1H-indole-2-carboxamide,
- ((3 S,4S)-3-Amino-4-methoxypyrrolidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone,
- 5-Chloro-6,7-difluoro-N-((3R,4 S)-4-methylpyrrolidin-3-yl)-1H-indole-2-carboxamide,
- ((3 S,4S)-3-Amino-4-fluoropyrrolidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone,
- (R)-(3-Aminopiperidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone,
- (S)-5-Chloro-6,7-difluoro-N-(piperidin-3-yl)-1H-indole-2-carboxamide,
- (R)-5-Chloro-6,7-difluoro-N-(piperidin-3-yl)-1H-indole-2-carboxamide,
- 5-Chloro-6,7-difluoro-N-((3R,4 S)-4-methylpiperidin-3-yl)-1H-indole-2-carboxamide,
- ((3 S,4S)-3-Amino-4-fluoropiperidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone, and
- ((3 S,4R)-3-Amino-4-fluoropiperidin-1-yl)(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone.
35 more elements
A compound, or pharmaceutically acceptable salt or solvate thereof, selected from:
- (S)-5-chloro-6,7-difluoro-N-methyl-N-(pyrrolidin-3-yl)-1H-indole-2-carboxamide,
- N-(azetidin-3-yl)-5-chloro-6,7-difluoro-N-methyl-1H-indole-2-carboxamide,
- 5-chloro-6,7-difluoro-N-(3-methylazetidin-3-yl)-1H-indole-2-carboxamide,
- 5-chloro-6,7-difluoro-N-((2 S, 3 S)-2-methylazetidin-3-yl)-1H-indole-2-carboxamide,
- 5-chloro-6,7-difluoro-N-((2R,3R)-2-methylazetidin-3-yl)-1H-indole-2-carboxamide,
- (1R,5S)-3,6-diazabicyclo[3.2.0]heptan-6-yl(5-chloro-6,7-difluoro-1H-indol-2-yl)methanone,
- (5-chloro-6,7-difluoro-1H-indol-2-yl)((3aS,6aS)-hexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl)methanone,
- (5-chloro-6,7-difluoro-1H-indol-2-yl)((3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl)methanone,
- (5-chloro-6,7-difluoro-1H-indol-2-yl)((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)methanone,
- (5-chloro-6,7-difluoro-1H-indol-2-yl)(2,6-diazaspiro[3.3]heptan-2-yl)methanone,
- (5-chloro-6,7-difluoro-1H-indol-2-yl)(2,6-diazaspiro[3.4]octan-2-yl)methanone,
- (S)-5-chloro-6,7-difluoro-N-(pyrrolidin-3-ylmethyl)-1H-indole-2-carboxamide,
- (R)-5-chloro-6,7-difluoro-N-(pyrrolidin-3-ylmethyl)-1H-indole-2-carboxamide,
- (S)-N-(1-aminopropan-2-yl)-5-chloro-6,7-difluoro-N-methyl-1H-indole-2-carboxamide,
- ((3 S,4S)-3-amino-4-hydroxypyrrolidin-1-yl)(5-bromo-6,7-difluoro-1H-indol-2-yl)methanone,
- ((3 S,4S)-3-amino-4-hydroxypyrrolidin-1-yl)(6,7-difluoro-5-iodo-1H-indol-2-yl)methanone, and
- ((3 S,4R)-3-amino-4-hydroxypyrrolidin-1-yl)(5-bromo-6,7-difluoro-1H-indol-2-yl)methanone.
14 more elements
Dependencies are inferred from the claim text.